Five hundred million people worldwide are infected with Toxoplasma gondii, up to 20 percent of the infected individuals develop ocular lesions, and some cases of ocular toxplasmosis are considered to be congenital with a late activation. To elucidate this question and to better understand the differences in the immune response between congenital and acquired infections we evaluated several immunological parameters in response to T. gondii in infected individuals with and without ocular lesions and in non-infected controls. Subjects were divided into four groups based on the presence of serum antibodies against T. gondii, presence of ocular lesions and clinical history. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of T. gondii (or control) antigens and proliferation was measured. Culture supernatants were assayed for a panel of cytokines. T cell receptor (TCR) expression was evaluated by flow cytometry or by reverse transcriptase polymerase chain reaction. Production of interleukin (IL)-2 and interferon (IFN)-gamma in response to T. gondii was lower in PBMCs of patients with congenital toxoplasmosis when compared to individuals with acquired infection with or without ocular lesions. PBMCs proliferation and delayed-type skin reaction induced by T. gondii antigens followed the same pattern. Asymptomatic individuals tended to have high IL-12 and IFN-gamma whereas individuals with ocular lesions had high IL-1 and tumor necrosis factor (TNF)-alpha responses to T. gondii. The data suggest that congenital infection results in immune tolerance to T. gondii and that susceptability is associated with high IL-1 and TNF-alpha, whereas resistance to acquired disease is associated with high IL-12 and IFN-gamma. TCR Vbeta expression was indistinquishable between the different groups.